Thymoquinone Preserves Pancreatic Islets Structure Through Upregulation of Pancreaticβ-Catenin in Hypothyroid Rats.
Diabetes Metab Syndr Obes. 2021 ;14:2913-2924. Epub 2021 Jun 29. PMID: 34234489
Background: Altered status of thyroid hormones, which have a key role in regulating metabolism, was reported to affect glucose homeostasis and insulin secretion.
Objective: This study was designed to assess the impact of propylthiouracil (PTU)-induced hypothyroidism on the pancreatic islet cells and the efficacy of thymoquinone (TQ) in alleviating this impact and explore the mechanism behind it alleviating oxidative stress and affectingβ-catenin expression.
Materials and Methods: PTU (6 mg/kg/body weight) was used to induce hypothyroidism in Wistar rats. Four groups of rats (n=6 each) were utilized in this study. Untreated hypothyroid and TQ-treated hypothyroid groups (50 mg/kg/body weight for 4 weeks) were included. Thyroid functions, antioxidant profile and pancreaticβ-catenin and IL-10 mRNA were measured. Histopathological and immunohistochemical assessment of the pancreas was performed.
Results: PTU administration induced a hypothyroid status that was associated with a marked disturbed oxidant/antioxidant status and a significant hyperglycemia (p<0:001), hypoinsulinemia (p=0.01) and decreased HOMA-β-cell (p<0.001). Islet cells of hypothyroid pancreas showed many degenerative changes with increased apoptosis, reduced insulinβ-catenin immunoexpression. Administration of TQ alleviated these effects on the thyroid function, antioxidants, structure of pancreatic islet cells. Up-regulation of β-catenin, IL-10 and CAT gene expression in pancreatic islets after treatment with TQ supported its antioxidant and preserving β-cell function and viability mechanistic action.
Conclusion: TQ alleviated PTU-induced hypothyroidism changes in insulin homeostasis and pancreaticβ cells mostly through its antioxidant effect as well as up-regulation of pancreatic β-catenin expression.